1. Field of the Invention
This invention relates to hyaluronidase compositions and methods for the effective treatment and prevention of pathogen infection, including retroviral infections such as HIV. The invention also relates to novel methods for developing and eliciting immune responses to pathogen infections, including retroviral infections such as HIV.
2. Description of the Related Art
Hyaluronidase enzymes are found throughout the animal kingdom and exist as hydrolytic, transglycosidic and mucolytic proteins. There are essentially two types of hyaluronidase: the non-specific type which breaks down hyaluronic acid, chondroitin and related polysaccharides; and the type which specifically cleaves hyaluronic acid. Hyaluronidases of varying molecular weights, composition, and activity are available from numerous sources including bacteria (via fermentation, etc.) various cell lines (including human) and animal testes.
Hyaluronidase has been used for the treatment of tumors (U.S. Pat. No. 6,193,963); for accelerating the clearance of hemorrhagic blood from the vitreous humor of the eye (U.S. Pat. No. 6,039,943); to reduce intraocular pressure in the eyes of glaucoma patients through degradation of hyaluronan within the vitreous humor (U.S. Pat. No. 4,820,516); as a “spreading agent” to enhance the activity of chemotherapeutics and/or the accessibility of tumors to chemotherapeutics (Czejka, et al., Pharmazie 1990, 45(9), 693–4); in the prevention and treatment of helmith infections (U.S. Pat. No. 5,811,100); and for treating benign prostatic hypertrophy (U.S. Pat. No. 5,116,615).
The primary substrate for the hyaluronidase enzyme is hyaluronic acid. Hyaluronic acid is a well known substance that is found in joint tissue and in the vitreous humor of the eye of mammals. Hyaluronic acid is also an integral part of many cell wall structures and has been extracted from rooster combs, human umbilical cords and bacterial cultures. It is a naturally occurring mucopolysaccharide with a molecular weight generally ranging between 50,000 and 8,000,000 (or possibly higher or lower), depending on the source of the material, the analytical method used in its determination and isolation technique.
The terms “haluronate” or “hyaluronan” and the abbreviation “HA” are often used to mean “hyaluronic acid equivalent” indicating hyaluronic acids of varying molecular weights, any of its salt forms, derivatives, isoforms, and/or ligand complexes.
The HIV virus utilizes hyaluronic acid in the adhesion process enabling the virus to bond to different cell lineages. For example, it has been reported that HIV can bind to hyaluronic acid through acquired CD44 adhesion molecules and its isoforms and retain its biological activity when expressed on the virus (J. Immunol. 1996, 156(4), 1557–1565; AIDS Res. Hum. Retroviruses 1995, 11(9), 1007–1113).
Described herein are hyaluronidase compositions and methods of using said compositions for the prevention and/or treatment of retroviral infections, such as HIV infection, in mammals.